The Importance of L-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice.

Sylwia Talarek, Joanna Listos, Jolanta Orzelska-Gorka, Malgorzata Jakobczuk, Jolanta Kotlinska, Grazyna Biala

Neurotoxicity research 2017 Feb

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The goal of the study was to investigate the effects of drugs modifying L-arginine:NO:cGMP pathway on the development of tolerance to flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: N G-nitro-L-arginine methyl ester (L-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: L-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.

Citation

Sylwia Talarek, Joanna Listos, Jolanta Orzelska-Gorka, Malgorzata Jakobczuk, Jolanta Kotlinska, Grazyna Biala. The Importance of L-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice. Neurotoxicity research. 2017 Feb;31(2):309-316